The present invention relates to a reactor plate and method for running multiple parallel screening reactions using multiphase reactant systems.
In experimental reaction systems, each potential combination of reactant, catalyst and condition must be evaluated in a manner that provides correlation to performance in a production scale reactor. Since about 1970, combinatorial organic synthesis (COS) has provided an important tool to address the requirements of experimental systems. COS is a systematic and repetitive synthesis that uses sets of chemical xe2x80x9cbuilding blocksxe2x80x9d to form a diverse set of molecular entities. As with traditional research, COS relies on organic synthesis methodology. However instead of synthesizing a single compound, COS exploits automation and miniaturization to synthesize large libraries of compounds; a procedure that can involve successive stages, each of which produces a chemical modification of an existing molecule of a preceding stage. The synthesis produces large numbers of diverse compounds, which can be screened for various activities.
In one approach to COS, arrayed, spatially addressable building blocks are reacted systematically on particle supports. The particles are distributed into a two-dimensional array so that each variant in a combinatorial library can be identified by its position in the array. The array can consist of a set of plates, each having rows and columns of wells, with one particle, or some other predetermined number of particles contained in each well. The particles are typically made of polystyrene. They serve as substrates for different compounds produced in the process of split and combine synthesis. Ultimately, synthesized compounds are stripped from the particles and tested for activity. The identity of an active compound can be determined by spectrographic analysis in the light of the information available concerning the reaction histories of the particles.
Combinatorial high throughput screening (CHTS) applies combinatorial chemistry principles of COS to the high throughput screening of materials and processes, particularly industrial materials and processes. A CHTS method can be characterized by parallel reactions at a micro scale. In one aspect, CHTS can be described as a method comprising (A) an iteration of steps of (i) selecting a set of reactants, conditions, catalysts or combinations thereof; (ii) reacting the set and (iii) evaluating a set of products of the reacting step. The CHTS method can further comprise (B) repeating the iteration of steps (i), (ii) and (iii) wherein a successive set of reactants, conditions, catalysts or combinations thereof, selected for a step (i) is chosen as a result of an evaluating step (iii) of a preceding iteration.
CHTS reactions are often conducted at elevated temperatures and at pressures both above and below atmospheric. Precise control of temperature can be critical for accurate evaluation of results. Precise control of temperature in each respective well may be part of a screening protocol. In this case, separate temperature control of each well may be required. In some CHTS systems, it may be necessary to repeatedly test within a precise and narrow range of temperatures. In this instance, the temperature ranges must be accurately duplicated in each well of an array as well as in repeated iterations of the CHTS protocol.
A uniformly heated array of wells may be obtained by placing a plate in a heated bath, oven or autoclave. But this mechanism does not address the problem of reactions that require different temperatures from well to well and can only poorly match temperatures from iteration to iteration. The wells can be individually wired and controlled with thermocouples or electromechanical or electronic controllers to provide different temperatures in different wells but these solutions are prohibitively expensive. There is a need for a reactor plate and method to provide separate effective and inexpensive heat control of respective plate wells for CHTS.
The present invention provides a reactor plate with wells that can be individually heated or that can be precisely repeatedly heated and a method that can provide individual and reproducible heat control of wells. According to the invention, a reactor plate comprises a substrate with an array of reaction wells and a ferromagnetic material included with the substrate.
In another embodiment, a CHTS method comprises providing a reactor plate comprising a substrate with an array of reaction wells and a ferromagnetic material responsive to the application of an electric field. The electric field is energized to control temperature in the proximity of at least one of the reaction wells.
In a final embodiment, a CHTS method comprises providing a reactor plate comprising an array of reaction wells and depositing a ferromagnetic object within at least one of the wells. The object is responsive to the application of an electric field. An electric field is then energized to control temperature in the reaction well.